The long range goal of this research is to elucidate mechanisms by which gonadotrophins (LH and FSH) and prostaglandins (PG) influence functions of ovarian follicles and corpora lutea (CL). Emphasis is placed on a recently described LH- an hCG-induced desensitization of adenylyl cyclase in follicles and CL to LH stimulation. Adenylyl cyclases from other tissues will be used as model systems when necessary. Studies on the physiology of the ovarian adenylyl cyclases will center on: a. development of hormonal responsiveness and hormonal control of desensitization by hCG in pregnant and pseudopregnant rats and rabbits; b. hormonal control of induction of LH response in rat follicles; c. role of cAMP mediating the desensitizing effect of hCG and LH; d. effect of LH on intrafollicular cAMP and cGMP and relation to its desensitizing effect; e. possibility that the PG-synthesizing action triggered by LH in rabbit follicles is mediated by a receptor distinct from that mediating adenylyl cyclase stimulation. Adenylyl cyclase will be determined after dissection and homogenization of the structures involved. Levels of reproductive hormones (estrogens, progestin, LH, FSH ad PRL) will be determined to allow for meaningful interpretation of the data. Studies on molecular aspects of LH action will be carried out primarily on membranes from pig Graafian follicles and will include: 1. solubilization, purification and characterization of components of the adenylyl cyclase system to determine architectural organization and develop a receptor assay based on reconstitution of hybrid particulate systems from solubilized components; 2. study of whether LH induces loss of its own action by phosphorylation of a component of the adenylyl cyclase system and purification of the component involved; 3. study of the relation of LH-specific binding to adenylyl cyclase activation; 4. studies on reversal of LH-induced desensitization; and 5. development of a CL system from which components can be isolated in large scale and initiation of large scale isolation of components identified in l. and 2.